APPLICANT'S ABSTRACT: The long range goal of this ongoing program of research is to find more effective treatments for alcohol dependence through combining medication with the appropriate psychosocial support. Naltrexone when used in conjunction with psychosocial therapy, reduces relapse to clinically significant drinking in compliant subjects. The present proposal extends our previous research by comparing the efficacy of naltrexone treatment administered in two types of primary care settings: one using simple medication management and a second using medication management with compliance enhancement techniques. In addition, we will compare these two conditions with cognitive behavioral therapy--a combination that has been successfully used to demonstrate naltrexone efficacy in prior research. This proposal has 3 specific aims: 1) To compare the effectiveness of naltrexone in 3 types of treatment settings; 2) Assess the effects of psychosocial support on medication compliance and treatment retention; and 3) To investigate the subject characteristics that may predict who is likely to benefit from additional psychosocial support versus simple medication management. To this end, 240 alcohol dependent outpatients who are, currently involved in outpatient alcohol rehabilitation at the University of Pennsylvania's Treatment Research Center will be randomly assigned to treatment with either naltrexone (100 mg per day) or placebo in double-blind fashion over a six-month period. Medication will be administered in three types of settings: 1) simple medication management by a research physician, 2) simple medication management plus Compliance Enhancement Techniques (CET) administered by a nurse practitioner, and 3) simple medication management plus Cognitive Behavioral Therapy (CBT) administered by a trained psychologist using the Project MATCH, CBT manual. The primary outcome measures are time to relapse to clinically significant drinking (5 or more in one day) and percent days of clinically significant drinking. Other alcohol use related measures include, alcohol craving, percent of abstinent days, and blood chemistries including liver enzymes. The outcome measures will be evaluated during the medication phase and at follow-up points 12 and 18 months after entrance into treatment. In addition, medication and treatment compliance will be evaluated during the trial. Medication compliance will be assessed by pill counts, urine screens for riboflavin and for those subjects on active medication by serum levels of naltrexone and beta-naltrexol. Treatment compliance will be evaluated by the percent of research visits attended. The results of this trial will provide important information on the clinical use of naltrexone in the treatment of alcohol dependence as alcohol dependence treatment moves into primary care settings.